Figure 9

Model of interplay between PARP-1, Sp1 and other transcription factors. (A) PARP-1 plays a suppressive function (indicated by 'T' bars) on the DNA binding properties of Sp1, and indirectly, on its expression as well, by the enzymatic addition of poly(ADP-ribose) units (PAR) to Sp1. PARP-1 may exert its effect by stimulating the transcriptional properties (indicated by arrows) of both AP-2 and E2F-1 by physically interacting with these transcription factors (and therefore, independently of addition of PAR), of which the latter was recognized as a component required to ensure proper transcription of the human Sp1 gene. (B) Once PARP-1 is stimulated by DNA damages, post-translational modification of both Sp1 and AP-2 is increased to the point that their DNA binding properties and thereby, their transcriptional capacity, is considerably decreased without significantly altering their level of expression. (C) However, in the absence of PARP-1, addition of PAR is abrogated and the transcriptional capacity of Sp1 becomes dramatically increased despite that its overall expression is considerably reduced primarily as a consequence of: i) a reduction in both the expression [112] and the positive transcriptional influence of E2F1 [85], a property that requires a physical interaction with PARP-1, and ii) a reduced transcriptional activity of AP-2, which also requires a physical association of this transcription factor with the middle region of PARP-1 [84]. TrC: transcriptional capacity of Sp1; Exp: level of Sp1 expression.